The Role of FER rs4957796 in the Risk of Developing and Dying from a Bloodstream Infection: A 23-Year Follow-up of the Population-based Nord-Trøndelag Health Study

Background: Bloodstream infection and sepsis are major causes of health loss worldwide, and it is important to identify patients at risk of developing and dying from these conditions. The single-nucleotide polymorphism most strongly associated with sepsis mortality is FER rs4957796. However, it is not known how this variant is associated with bloodstream infection incidence and mortality.

Methods: We used prospective data from 1995-2017 from the population-based HUNT Study. Genotypes were ascertained from blood samples, and additional genotypes were imputed. Information on bloodstream infection and diagnosis codes at hospitalization were collected through record linkage with all hospitals in the area.

Results: A total of 69 294 patients were included. Patients with the rs4957796 CC genotype had an increased risk of developing a bloodstream infection compared with the TT genotype (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.00-1.43). However, there was a protective additive effect of the C allele in terms of mortality in the total study population (HR, 0.77; 95% CI, .64-.92 per copy of the C allele) and among bloodstream infection patients (odds ratio, 0.70; 95% CI, .58-.85 per copy of the C allele). The results did not appear to be affected by selection bias.

Conclusions: The rs4957796 CC genotype was associated with an increased risk of contracting a bloodstream infection but with a reduced risk of dying from one. The latter finding is in line with studies of sepsis case fatality, while the former expands our understanding of the immunoregulatory role of this polymorphism.

Keywords: FER tyrosine kinase; bacteremia; genetic association studies; prospective studies; sepsis.